There has been relatively little improvement in pre-hospital therapy compared to the dramatic advances in therapy after arriving to the hospital. The addition of a potent aIIbB3 antagonist administered alongside standard oral aspirin in the pre-hospital therapy of patients with ST segment-elevated myocardial infarction (STEMI) has the potential to decrease early mortality and the development of congestive heart failure during the next 6-12 months. This hypothesis is based on evidence showing that therapy with other aIIbB3 antagonists (along with aspirin) soon after symptom onset can abort the progression of thrombotic myocardial ischemia to irreversible cardiac damage and decrease mortality. Moreover, we expect a favorable safety profile since patients will neither be anticoagulated nor undergo arterial access in the pre-hospital setting, and the effects will wear off within 2-4 hours. The current aIIbB3 antagonists all must be administered intravenously, a major disadvantage for pre-hospital therapy. We currently are gathering the needed Investigational New Drug (IND)-enabling data to advance RUC-4, a novel aIIbB3 antagonist, to human studies. Based on crystallographic structural studies of aIIbB3, RUC-4 was designed to be specific for aIIbB3 and to have a unique mechanism of action that not only prevents ligand binding, but also prevents the conformational changes in the 3 subunit induced by current aIIbB3 antagonists patterned on the R(K)GD sequence that have been implicated in causing thrombocytopenia and paradoxical receptor activation. RUC-4 was also designed to have high solubility (80 mg/ml) so that the likely human dose (1 mg/kg) can be administered in 1 ml by autoinjector. Based on studies in mice and non-human primates, RUC-4 is rapidly absorbed after intramuscular injection. In non-human primates, platelet aggregation was eliminated within 15 minutes after a 0.27 ml IM dose of 1.93 mg/kg with partial return of platelet aggregation after 4.5 hours. A lower dose (0.47 ml; 1 mg/kg) produced partial inhibition of aggregation at 15 minutes, complete inhibition at 30 minutes, and partial return of aggregation at 2 hours. Thus, the current profile for RUC4 matches the anticipated needs for a pre-hospital therapy of patients with ST segment-elevated myocardial infarction (STEMI).